Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR |
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Authors: | Reaper Philip M Griffiths Matthew R Long Joanna M Charrier Jean-Damien Maccormick Somhairle Charlton Peter A Golec Julian M C Pollard John R |
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Affiliation: | Vertex Pharmaceuticals (Europe), Abingdon, Oxfordshire, UK. |
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Abstract: | Here we report a comprehensive biological characterization of a potent and selective small-molecule inhibitor of the DNA damage response (DDR) kinase ATR. We show a profound synthetic lethal interaction between ATR and the ATM-p53 tumor suppressor pathway in cells treated with DNA-damaging agents and establish ATR inhibition as a way to transform the outcome for patients with cancer treated with ionizing radiation or genotoxic drugs. |
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